CD19 CART Cells for Patients With Relapse and Refractory CD19+ B-cell Lymphoma.

Phase I/II Study of CD19 CART Cells for Patients With Relapse and Refractory CD19+ B-cell Lymphoma.

This is a clinical study to observe the maximum tolerated dose (MTD) and the safety and feasibility of chimeric antigen receptor 19 (CD19 CART) cells in relapsed and refractory patients with CD19+ B cell lymphoma.

Study Overview

• Status: Unknown
• Conditions: B Cell Lymphoma
• Intervention / Treatment: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: CD19 CART

Detailed Description

This is a study for the patients with B cell lymphoma. Maximum tolerated dose climbing test is expected into the group of 9 cases of patients. And Phase II expected into the group of 11 subjects, selected the above safe dose, carrying out a research into the clinical effectiveness. Subjects will be collected their T cells and modify them, the modification is a genetic change, that CD19:4-1BB:CD28:CD3 modified T cells, in order to tells the T cells to recognize their target tumor cells and potentially kill them, but not other normal cells in the subject's body. The CART cells will then be expanded in vitro and then administered to subjects. The purpose of this study is observe the MTD and to assess the safety and feasibility of CART cells in the patients with relapsed and refractory CD19+ B cell lymphoma.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: geng tian; Phone Number: 13724395569; Email: tiangeng666@aliyun.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China
      • Recruiting
      • The second people's Hospital of Shenzhen
      • Contact: geng tian; Phone Number: 13724395569; Email: tiangeng666@aliyun.com
      • Principal Investigator: geng tian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. 18 years to 70 years, expected survival > 3 months;
• 2. CD19 positive B-cell lymphoma;
• 3. KPS >80;
• 4. Having at least one measurable lesions;
• 5. Cardiac function: 1-2 levels; Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN; kidney: Cr≤1.25ULN; bone marrow: WBC ≥ 3.0×109/L, Hb ≥90 g/L, PLT ≥ 80×109/L）;
• 6. No serious allergic constitution;
• 7. No other serous diseases that conflicts with the clinical program;
• 8. No other cancer history;
• 9. No serious mental disorder;
• 10. Informed consent is signed by a subject or his lineal relation.

Exclusion Criteria:

• 1. Pregnant or lactating women; (female participants of reproductive potential must have a negative serum or urine pregnancy test);
• 2. Uncontrolled active infection, HIV infection, syphilis serology reaction positive;
• 3. Active hepatitis B or hepatitis C infection;
• 4. Recent or current use of glucocorticoid or other immunosuppressor;
• 5. With severe cardiac, liver, renal insufficiency, diabetes and other diseases;
• 6. Transaminase >2.5ULN, Bilirubin >3ULN，Creatinine>1.25ULN
• 7. Participate in other clinical research in the past three months; previously treatment with any gene therapy products;
• 8. Researchers think of that does not fit to participate in the study, or other cases that affect the clinical trial results;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CD19 CART; patients will receive a pre-conditioning with cyclophosphamide and fludarabine before infusion of CD19 CART cells. The CD19 CART cells are to be administered on day0,day1,day2.	Drug: Fludarabine; Fludarabine 30 mg/m2/day IV for 3 days.; Drug: Cyclophosphamide; patients will receive a standard pre-conditioning regime with cyclophosphamide 0.8g/m2/day IV for 2 days.; Biological: CD19 CART; CD19 CART cells will be administered using a split dose on day0(10%), 1(30%), and 2(60%) after completion of the chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety as assessed by the occurence of study related adverse events	monitor the occurence of study related adverse events	6 months
Progression-Free Survival		2 years
observe the maximum tolerated dose (MTD)		2 months
objective response rate	CR+PR	2 years
disease control rate	CR+PR+SD	2 years
overall survival	OS	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine duration of in vivo survival of CD19 CART cells	CD19 CART vector sequences will be performed by Q-PCR	2 years
Peripheral blood cytokines	IL-6、IL-10、IFN-γ、TNF-α	2 months
subgroup of T cell	CD3、CD4、CD8	2 years

Collaborators and Investigators

• Sponsor: Shenzhen Second People's Hospital
• Collaborators: The Beijing Pregene Science and Technology Company, Ltd.
• Investigators: Principal Investigator: geng tian, Shenzhen Second People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2017
• Primary Completion (Anticipated): April 1, 2019
• Study Completion (Anticipated): October 1, 2019

Study Registration Dates

• First Submitted: May 7, 2017
• First Submitted That Met QC Criteria: May 7, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: FirstShenzhen01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No